We have shown that p53 balances the energy generated by respiration and glycolysis and promotes aerobic metabolism through it positive regulation of mitochondrial function. An interesting effect of this biological mechanism is that mice deficient in p53 display profound deficiencies in aerobic exercise capacity. Given the strong inverse relationship between exercise capacity and cancer incidence in large epidemiologic studies, we are characterizing the regulation of mitochondrial function by p53 as a tumor suppressor and the relation between cardiovascular exercise capacity and tumorigenesis using mouse models and human studies. Specifically, we are studying cardiovascular and metabolic functions in individuals with Li-Fraumeni syndrome, a premature cancer syndrome caused by germline mutations in the p53 gene. The goal of this research is to derive basic insights that may assist in the development of new strategies for preventing cancer and improving cardiovascular fitness.